Rescue Me revolves around the lives of the men in a New York City firehouse, the crew of 62 Truck. Examining the fraternal nature and relationships of firefighters, the series tackles the daily drama of the life-and-death situations associated with being a firefighter, while exploring the ways the men use dark humor to protect their true emotions.

After taking his dying father's advice, Hal dates only the embodiments of female physical perfection. But that all changes after Hal has an unexpected run-in with self-help guru Tony Robbins. Intrigued by Hal's shallowness, Robbins hypnotizes him into seeing the beauty that exists even in the least physically appealing women. Hal soon falls for Rosemary, but he doesn't realize that his gorgeous girlfriend is actually a 300-pound-not-so-hottie.

Bobby O'Grady is a low level member of a Boston Irish gang run by Jackie O'Hara. Jackie demands absolute, total loyalty to him. When Jackie kills one of Bobby's buddies, Teddy, Bobby and others have to keep it an absolute secret, even from their and Teddy's relatives.